The post of Secretary of State for Wales came into existence on 17 October 1964; the first incumbent was Jim Griffiths, MP for Llanelli. The position entailed responsibility for Wales, and expenditure on certain public services was delegated from Westminster. In April 1965 administration of Welsh affairs, which had previously been divided between a number of government departments, was united in a newly created Welsh Office with the Secretary of State for Wales at its head, and the Welsh Secretary became responsible for education and training, health, trade and industry, environment, transport and agriculture within Wales.

During the 1980s and 1990s, as the number of Conservative MPs for Welsh constituencies dwindled almost to zero, the office fell into disrepute. Nicholas Edwards, MP for Pembrokeshire, held the post for eight years. On his departure, the government ceased to look within Wales for the Secretary of State, and the post was increasingly used as a way of getting junior high-fliers into the Cabinet. John Redwood in particular caused embarrassment when he publicly demonstrated his inability to sing Hen Wlad Fy Nhadau", the Welsh national anthem, at a conference.

The introduction of the National Assembly for Wales and the Welsh Government, after the devolutionreferendum of 1997, was the beginning of a new era. On 1 July 1999 the majority of the functions of the Welsh Office transferred to the new assembly. The Welsh Office was disbanded, but the post of Secretary of State for Wales was retained, as the head of the newly created Wales Office.